LAUSR

Oscillatory synchronization at low frequencies (<15 Hz) is a powerful mechanism by which neural networks coordinate their activities. Slow oscillations are transmitted with minor phase delay between distant brain regions, and thus provide a flexible signal to synchronize neuronal firing and locally generated fast (high beta, gamma) oscillations in these structures (Buzsaki 2002). In particular, rhythmic synchronizations of hippocampus (HC) and prefrontal cortex (PFC) are thought to mediate key cognitive functions, such as working memory (Benchenane et al. 2010; Sauseng et al. 2010; Anderson et al. 2010; Hyman et al. 2005) or goal-directed spatial navigation (Ito et al. 2015). Disruptions in HC-PFC coupling may mediate some of the pathophysiology of schizophrenia (Cousijn et al. 2015; Dickerson et al. 2010; Sigurdsson et al. 2010; Vertes 1981). The overwhelming majority of prior studies emphasized the role of PFC–HC coupling at theta frequency (Anderson et al. 2010; Benchenane et al. 2010; O’Neill et al. 2013; Sauseng et al. 2010; Siapas et al. 2005; Jones and Wilson 2005; Hyman et al. 2005). Theta rhythm is the most prominent oscillatory signal in the rodent brain generated by the septo-hippocampal network (Buzsaki 2002; Vertes and Kocsis 1997), and thus theta coupling tacitly assumes driving by the HC. Since, however, PFC is thought to play a key Abstract Rhythmic synchronizations of hippocampus (HC) and prefrontal cortex (PFC) at theta frequencies (4–8 Hz) are thought to mediate key cognitive functions, and disruptions of HC-PFC coupling were implicated in psychiatric diseases. Theta coupling is thought to represent a HC-to-PFC drive transmitted via the well-described unidirectional HC projection to PFC. In comparison, communication in the PFC-to-HC direction is less understood, partly because no known direct anatomical connection exists. Two recent findings, i.e., reciprocal projections between the thalamic nucleus reuniens (nRE) with both PFC and HC and a unique 2–5 Hz rhythm reported in the PFC, indicate, however, that a second low-frequency oscillation may provide a synchronizing signal from PFC to HC via nRE. Thus, in this study, we recorded local field potentials in the PFC, HC, and nRE to investigate the role of nRE in PFC–HC coupling established by the two low-frequency oscillations. Using urethane-anesthetized rats and stimulation of pontine reticular formation to experimentally control the parameters of both forebrain rhythms, we found that theta and 2–5 Hz rhythm were dominant in HC and PFC, respectively, but were present and correlated in all three signals. Removal of nRE influence, either statistically (by partialization of PFC–HC correlation when controlling for the nRE signal) or pharmacologically (by lidocaine microinjection in nRE), resulted in decreased coherence between the PFC and HC 2–5-Hz oscillations, but had minimal effect on theta coupling. This study proposes a novel